This study seeks to determine efficacy of the calpain inhibitor, leupeptin, in the treatment of Duchenne muscular dystrophy (DMD) using a canine model. Data indicate that calpains play an important role in the pathogenesis of DMD. Accordingly, calpain inhibition may provide therapeutic benefit to patients. Our preliminary study in young dogs with canine muscular dystrophy suggests clinical benefit from oral leupeptin. We intent to extend these experiments using functional measures to assess leupeptin's potential as a treatment modality for humans with DMD. The specific aims are to: Specific Aim #1a: Evaluate efficacy of oral leupeptin (30mg/kg daily from 1-3 months of age) on muscle function as assessed by maximal isometric force in GRMD dogs. Specific Aim #1b: Evaluate efficacy of oral leupeptin (30mg/kg daily, 1- 3 months of age) on clinical disease progression as measured by tarsal joint angles in GRMD dogs. Specific Aim #2: Evaluate efficacy of oral leupeptin (SOmg/kg daily from 1- 3 months of age) on muscle damage and necrosis in a canine model of DMD as assessed by contraction-induced force deficit and histologic evaluation of muscle biopsies Specific Aim #3: Evaluate safety of daily oral leupeptin (30 mg/kg) in GRMD dogs. Specific Aim #4a: Determine serum bioavailability of oral leupeptin (30mg/kg) in GRMD dogs using mass spectral analysis. Specific Aim #4b: Compare lean body muscle mass and calpain activity between leupeptin and placebo-treated GRMD dogs.